Sarah Gilbert: paving the way for a COVID-19 vaccine

It was the news from Wuhan, China, in the early days of 2020 that made Sarah Gilbert sit and think. As a professor of vaccinology at Oxford University in the UK and a leading scientist at the university’s Jenner Institute, her research team wasted no time in getting involved. “We recently started thinking about an adequate response to disease X; How could we mobilize and focus our resources to go faster than ever? And then disease X came, ”she says. Once the severe acute respiratory syndrome coronavirus 2 genome sequence (SARS-CoV-2) became available in mid-January, Gilbert’s team set to work to design a vaccine, using recombinant DNA techniques to create a SARS-CoV-2 antigen and embedding within a primate adenovirus vector. “At this point, everything seemed quite theoretical, our goal was to design a vaccine and publish a document that showed what was possible in terms of a rapid response to an unknown outbreak, using our adenoviral vectorized vaccine technology,” he says.

Gilbert’s team received a £ 2 · 2 million grant from the UK National Institute for Health Research and UK Research and Innovation in March 2020, to scale up their team’s efforts to advance towards the preclinical vaccine and The Coronavirus Disease Vaccine 2019 (COVID-19) clinical trials. “The way in which various grants have been awarded to different strategic aspects of the project is important, since much of the work can continue in parallel; for example, my colleague Sandy Douglas has received funding to work on expanding vaccine manufacturing processes at the same time as we move forward on trial development work, “she says. Preclinical work at the Porton Down facility Public Health England’s is the immediate priority, complementing parallel initiatives taking place at the US National Institutes of Health and the Commonwealth Scientific and Industrial Research Organization in Australia, among others. Gilbert’s team received ethical approval for a clinical trial, and conditional approval from the UK Medicines and Health Products Regulatory Agency to evaluate volunteers for trial enrollment. Another reason for speed is for your team to evaluate the effectiveness of a vaccine in volunteers who have not yet been infected. “Ideally, we need the clinical trial to be conducted c When most of the volunteers have not been exposed to the virus. We will exclude volunteers who have a positive PCR test for SARS-CoV-2, or who have had a fever or cough in the past month. Inevitably, some will have been exposed, and that is also helpful, as we want to know what the vaccine means for people who have been exposed to the coronavirus, ”she says.

Gilbert’s initial vaccine work at Oxford University began in 1994 with Adrian Hill, who is now Director of the Jenner Institute, with a focus on malaria vaccine research and, given his particular interest in cellular immunology, the importance of T cell responses to parasitic infection. “From what we were seeing in malaria endemic regions, people with a specific type of HLA performed better after becoming infected with malaria than others with different HLA profiles. This led us to consider creating vaccine candidates that could trigger favorable T-cell responses, rather than relying solely on antibody responses, the prevailing vaccine model at the time, “he explains. This approach coincided with advances in recombinant DNA techniques, with vaccinologists capable of generating specific antigens that could be safely incorporated into a host virus, as an alternative to the risks associated with the use of live attenuated vaccines. The ability to create recombinant viral vector vaccines is a central function of Gilbert’s research group at the Jenner Institute, which has progressed work on many vaccines in recent years, including influenza virus and Zika virus vaccines. and early-stage trials for the Middle East respiratory syndrome coronavirus vaccine, a useful template for work on a COVID-19 vaccine. As chair of the management committee that oversees initial vaccine production within the University of Oxford, Gilbert and his colleagues have suspended all other concurrent vaccine investigations to prioritize efforts at COVID-19.

Gilbert is understandably cautious when asked to plan a timeline for the trial, but he hopes to have vaccinated 500 volunteers in mid-May; This will be followed by an extension of the maximum age of the test volunteers from 55 to 70 years, before moving on to the group of over 70 years. The Phase 3 expansion is expected to involve 5,000 volunteers; The results of the above trials will be included in the efficacy monitoring. “The best case scenario is that by fall 2020, we have a Phase 3 efficacy result and the ability to manufacture large quantities of the vaccine, but these timelines are the most ambitious and subject to change,” says Gilbert. . “Our ability to determine vaccine efficacy will be affected by the amount of virus transmission in the local population during the summer, and we are also beginning to think about starting trials with partners in other countries to increase our ability to determine efficacy. of the vaccine, “he said. He says.

Sharing knowledge with parallel efforts of the COVID-19 vaccine worldwide is crucial. “WHO is in the process of creating a forum for all who are developing COVID-19 vaccines to meet and present their initial plans and results. It is essential that we all measure immune responses to various vaccines in the same way, to ensure comparability and generalization of our collective findings. Work continues at a very fast pace, and I have no doubt that we will see an unprecedented spirit of collaboration and cooperation, convened by WHO, as we move towards a shared global goal of preventing COVID-19 through vaccination. Gilbert says.